The objective of this proposal is to define the immunoregulatory role of human gangliosides (sialic acid-containing glycosphingolipids). The studies are designed to determine the role of gangliosides in normal immunoregulation and in the immunosupression frequently associated with cancer. Tumor cell culture supernatants and cancer patient plasmas will be initially screened for inhibitory effects in the lmphocyte blastogenesis assay. Gangliosides will be isolated from the inhibitory samples, normal plasma, and normal human lipoproteins and similarly tested. Ganglioside isolation will be facilitated by the newly-developed techniques of thin layer chromatography which enable the non-destructive isolation and separation of individual gangliosides from small (1-2ml) quantities of the supernatants or plasma. This allows simple and rapid isolation of immunoregulatory gangliosides. The mechanisms by which immunoregulatory gangliosides exert their effects on lymphocyte blastogenic responses will be studied. Effects on the macrophage and T cell will be defined. Selected active gangliosides will be isolated in quantities for structural identification and structure-function studies. An animal model will be utilized to determine the modulatory effect of tumor cell-derived gangliosides on the host immune response to syngeneic tumor in vivo. The isolation and testing of gangliosides shed by tumor cells will define their effects on the immune system in cancer. The studies of normal lipoprotein-associated gangliosides will define the contribution of these gangliosides to the documented immunoregulatory functions of normal lipoproteins. The results of the proposed work will contribute to our long-term objective of fully characterizing the immunoregulatory role of human gangliosides in health and disease.